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Effect of Epidural Bupivacaine Block on Midazolam Hypnotic Requirements
  1. Mark Tverskoy, M.D., Ph.D.*,
  2. Vitaly Shifrin, M.D.*,
  3. Jacob Finger, M.D.*,
  4. Grigory Fleyshman, M.D.* and
  5. Igor Kissin, M.D., Ph.D.
  1. *Department of Anesthesiology, Rebecca Sieff Hospital, Safed, Israel, and the
  2. Department of Anesthesia, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
  1. Reprint requests: Dr. Igor Kissin, Department of Anesthesia, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115.


Background and Objectives The aim of the study was to determine the effect of epidural bupivacaine block on midazolam hypnotic requirements.

Methods Sixty unpremedicated, ASA physical status I or II male patients, aged 45-65 years and scheduled for elective lower abdominal, pelvic, or lower limb surgery participated in this randomized, double-blind, placebo-controlled study. The study population was composed of three groups: Before administration of midazolam, patients in the first group received an intramuscular injection of 15 mL saline (M), those in the second group an intramuscular injection of 15 mL 0.5% bupivacaine (MIB), and those in the third group an epidural injection of 15 mL 0.5% bupivacaine at the L3-L4 level (MEB). Loss of the ability to respond to verbal command was used as an endpoint for the effect of midazolam injected intravenously in predetermined doses (five patients per dose) 30 minutes after a bupivacaine (or saline) injection. Midazolam dose-response curves were obtained by probit analysis.

Results The midazolam median effective dose values for the hypnotic effect were 0.20 mg/kg (95% confidence limit, 0.10-0.27 mg/kg) in the M group; 0.10 mg/kg (0.06-0.22 mg/kg) in the MIB group; and 0.04 mg/kg (0.03-0.07 mg/kg) in the MEB group. The differences between the midazolam median effective dose values had high levels of significance: P < .00001 for MEB versus M, P < .002 for MEB versus MIB, and P < .01 for MIB versus M.

Conclusions Epidural bupivacaine block profoundly decreases midazolam hypnotic requirements. The most likely explanation for this effect is the reduction in afferent input induced by the block.

  • epidural anesthesia
  • intravenous midazolam anesthetic
  • local bupivacaine anesthetic

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